Endothelin-1 Quantikine ELISA

Total Page:16

File Type:pdf, Size:1020Kb

Endothelin-1 Quantikine ELISA Quantikine™ ELISA Endothelin-1 Immunoassay Catalog Number DET100 Catalog Number SET100 Catalog Number PDET100 For the quantitative determination of Endothelin-1 concentrations in cell culture supernates, serum, plasma, and urine. This package insert must be read in its entirety before using this product. For research use only. Not for use in diagnostic procedures. TABLE OF CONTENTS SECTION PAGE INTRODUCTION ....................................................................................................................................................................1 PRINCIPLE OF THE ASSAY ..................................................................................................................................................2 LIMITATIONS OF THE PROCEDURE ................................................................................................................................2 TECHNICAL HINTS ................................................................................................................................................................2 MATERIALS PROVIDED & STORAGE CONDITIONS ..................................................................................................3 PHARMPAK CONTENTS ......................................................................................................................................................4 OTHER SUPPLIES REQUIRED ............................................................................................................................................5 PRECAUTIONS ........................................................................................................................................................................5 SAMPLE COLLECTION & STORAGE ................................................................................................................................6 REAGENT PREPARATION ....................................................................................................................................................7 ASSAY PROCEDURE ............................................................................................................................................................8 CALCULATION OF RESULTS ..............................................................................................................................................9 TYPICAL DATA ........................................................................................................................................................................9 PRECISION ............................................................................................................................................................................ 10 RECOVERY............................................................................................................................................................................. 10 SENSITIVITY ......................................................................................................................................................................... 10 LINEARITY ............................................................................................................................................................................. 11 CALIBRATION ...................................................................................................................................................................... 12 SAMPLE VALUES ................................................................................................................................................................. 12 SPECIFICITY .......................................................................................................................................................................... 13 REFERENCES ........................................................................................................................................................................ 13 Manufactured and Distributed by: USA R&D Systems, Inc. 614 McKinley Place NE, Minneapolis, MN 55413 TEL: 800 343 7475 612 379 2956 FAX: 612 656 4400 E-MAIL: [email protected] Distributed by: Europe | Middle East | Africa Bio-Techne Ltd. China Bio-Techne China Co., Ltd. 19 Barton Lane, Abingdon Science Park Unit 1901, Tower 3, Raffles City Changning Office, Abingdon OX14 3NB, UK 1193 Changning Road, Shanghai PRC 200051 TEL: +44 (0)1235 529449 TEL: +86 (21) 52380373 (400) 821-3475 FAX: +44 (0)1235 533420 FAX: +86 (21) 52371001 E-MAIL: [email protected] E-MAIL: [email protected] INTRODUCTION Endothelin-1 (ET-1), a peptide of 21 amino acid (aa) residues, is a pleiotropic molecule best known for its action as a potent vasoconstrictor (1). Originally isolated from porcine aortic endothelial cells, ET-1 is one of a family of three proteins encoded by distinct genes that also includes Endothelin-2 (ET-2) and Endothelin-3 (ET-3) (2, 3). ET-2 and ET-3 differ from ET-1 by 2 and 6 amino acids, respectively (1, 2). All members of the Endothelin family contain two essential disulfide bridges and six conserved aa residues at the C-terminus. Human ET-1 is initially synthesized as a pre-pro-polypeptide of 212 amino acids (2, 4). It is proteolytically cleaved by a signal peptidase to produce pro-ET-1 and further processed by a Furin-like protease to yield a 38 aa peptide termed Big ET-1 (5, 6). Big ET-1 is then cleaved by the membrane-bound metalloprotease Endothelin-converting enzyme (ECE-1), producing the potent 21 aa mature form ET-1 (aa 1-21) (7, 8). Alternatively, ET-1 may exist in an active 31 aa form (ET-1 (aa 1-31)) following cleavage of Big ET-1 by chymase (9-12). The vascular endothelium is an abundant source of ET-1 (3, 13). It may also be expressed by leukocytes, smooth muscle cells, mesangial cells, cardiac myocytes, and astrocytes (14, 15). ET-1 can be induced in endothelial cells by many factors including mechanical stimulation, various hormones, and pro-inflammatory cytokines (16). Production is inhibited by nitric oxide (NO), Prostacyclin, and atrial natriuretic peptide (ANP) (17-19). Two receptors for the Endothelin family have been cloned and designated ETA and ETB (20-23). ETA and ETB belong to the large family of heptahelical G protein-coupled receptors. The ETA receptor shows a higher affinity for ET-1 than for ET-2 and lowest affinity for ET-3, while the ETB receptor shows approximately equal affinity for each of the three Endothelins (21, 22, 24). ETA is primarily responsible for the vasoconstrictor effects of ET-1 and is expressed by blood vessel smooth muscle cells (25, 26). The ETB receptor is also present in smooth muscle and the endothelia of blood vessels, kidney, lung, and brain (27). ET-1 has the ability to activate an array of signaling cascades including classical phosphatidylinositol turnover pathways leading to downstream PKC activation and Ca2+ mobilization (28-32). Other potential signaling mediators activated or produced by ET-1 include PI 3-kinase/Akt, NO, FAK, and Rho GTPases (32-37). ET-1 signaling may also be mediated indirectly via transactivation of the EGF receptor leading to downstream signaling by Ras and MAP kinases (38, 39). Injection of a single dose of ET-1 produces an initial decrease in systemic blood pressure followed by a prolonged increase in blood pressure (16, 40, 41). Blockade of Endothelin receptors with a systemic injection of an ETA/ETB antagonist causes progressive vasodilation, and elevated levels of ET-1 are found in some forms of human hypertension (42, 43). ET-1 also stimulates cardiac contraction and the growth of cardiac myocytes, regulates the release of vasoactive substances, and stimulates smooth muscle cell mitogenesis (32, 44-46). It also acts as a pro-survival factor for endothelial cells and regulates secretion by hypothalamic and pituitary cells (47, 48). ET-1 may control inflammatory responses by promoting the adhesion and migration of neutrophils and stimulating the production of pro-inflammatory cytokines (49-53). It has also been implicated in cancer progression at several levels including regulating the proliferation and migration of tumor cells and acting as a pro-angiogenic factor (54, 55). In addition, ET-1 has putative roles in other pathologies including septic shock, atherosclerosis, heart failure, renal insufficiency, pulmonary hypertension, and cerebrovascular conditions associated with subarachnoid hemorrhage (15, 56-63). The Quantikine™ Endothelin-1 immunoassay is a 4.5 hour solid phase ELISA designed to measure ET-1 in cell culture supernates, serum, plasma, and urine. It contains synthetic ET-1 and antibodies raised against synthetic ET-1. This immunoassay has been shown to accurately quantitate synthetic and natural ET-1. www.RnDSystems.com 1 PRINCIPLE OF THE ASSAY This assay employs the quantitative sandwich enzyme immunoassay technique. A monoclonal antibody specific for Endothelin-1 has been pre-coated onto a microplate. Standards and samples are pipetted into the wells and any Endothelin-1 present is bound by the immobilized antibody. After washing away any unbound substances, an enzyme-linked monoclonal antibody specific for Endothelin-1 is added to the wells. Following a wash to remove any unbound antibody-enzyme reagent, a substrate solution is added to the wells and color develops in proportion to the amount of Endothelin 1 bound in the initial step. The color development is stopped and the intensity of the color is measured. LIMITATIONS
Recommended publications
  • Cellular Responses to Erbb-2 Overexpression in Human Mammary Luminal Epithelial Cells: Comparison of Mrna and Protein Expression
    British Journal of Cancer (2004) 90, 173 – 181 & 2004 Cancer Research UK All rights reserved 0007 – 0920/04 $25.00 www.bjcancer.com Cellular responses to ErbB-2 overexpression in human mammary luminal epithelial cells: comparison of mRNA and protein expression SL White1, S Gharbi1, MF Bertani1, H-L Chan1, MD Waterfield1 and JF Timms*,1 1 Ludwig Institute for Cancer Research, Wing 1.1, Cruciform Building, Gower Street, London WCIE 6BT, UK Microarray analysis offers a powerful tool for studying the mechanisms of cellular transformation, although the correlation between mRNA and protein expression is largely unknown. In this study, a microarray analysis was performed to compare transcription in response to overexpression of the ErbB-2 receptor tyrosine kinase in a model mammary luminal epithelial cell system, and in response to the ErbB-specific growth factor heregulin b1. We sought to validate mRNA changes by monitoring changes at the protein level using a parallel proteomics strategy, and report a surprisingly high correlation between transcription and translation for the subset of genes studied. We further characterised the identified targets and relate differential expression to changes in the biological properties of ErbB-2-overexpressing cells. We found differential regulation of several key cell cycle modulators, including cyclin D2, and downregulation of a large number of interferon-inducible genes, consistent with increased proliferation of the ErbB-2- overexpressing cells. Furthermore, differential expression of genes involved in extracellular matrix modelling and cellular adhesion was linked to altered adhesion of these cells. Finally, we provide evidence for enhanced autocrine activation of MAPK signalling and the AP-1 transcription complex.
    [Show full text]
  • Endothelin-2 Signaling in the Neural Retina Promotes the Endothelial Tip Cell State and Inhibits Angiogenesis
    Endothelin-2 signaling in the neural retina promotes PNAS PLUS the endothelial tip cell state and inhibits angiogenesis Amir Rattnera,1, Huimin Yua, John Williamsa,b, Philip M. Smallwooda,b, and Jeremy Nathansa,b,c,d,1 Departments of aMolecular Biology and Genetics, cNeuroscience, and dOphthalmology and bHoward Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Contributed by Jeremy Nathans, August 20, 2013 (sent for review February 19, 2013) Endothelin signaling is required for neural crest migration and time lapse imaging studies of vascular development in zebrafish homeostatic regulation of blood pressure. Here, we report that and mammalian EC dynamics in explant culture show that the tip constitutive overexpression of Endothelin-2 (Edn2) in the mouse cell and stalk cell states are highly plastic, with frequent retina perturbs vascular development by inhibiting endothelial cell exchanges between the two cell states (8, 9). migration across the retinal surface and subsequent endothelial Several other signaling pathways are also essential for retinal cell invasion into the retina. Developing endothelial cells exist in vascular development. Norrin, a Muller-glia–derived ligand, and one of two states: tip cells at the growing front and stalk cells in its EC receptor Frizzled4 (Fz4), coreceptor Lrp5, and receptor the vascular plexus behind the front. This division of endothelial chaperone Tspan12 activate canonical Wnt signaling in de- cell states is one of the central organizing principles of angiogen- veloping ECs (10). In humans and mice, defects in any of these esis. In the developing retina, Edn2 overexpression leads to components lead to retinal hypovascularization.
    [Show full text]
  • ADIPOR1 Is Essential for Vision and Its RPE Expression Is Lost in the Mfrp Valentin M Sluch
    The Jackson Laboratory The Mouseion at the JAXlibrary Faculty Research 2018 Faculty Research 9-25-2018 ADIPOR1 is essential for vision and its RPE expression is lost in the Mfrp Valentin M Sluch Angela Banks Hui Li Maura A Crowley Vanessa Davis See next page for additional authors Follow this and additional works at: https://mouseion.jax.org/stfb2018 Part of the Life Sciences Commons, and the Medicine and Health Sciences Commons Recommended Citation Sluch, Valentin M; Banks, Angela; Li, Hui; Crowley, Maura A; Davis, Vanessa; Xiang, Chuanxi; Yang, Junzheng; Demirs, John T; Vrouvlianis, Joanna; Leehy, Barrett; Hanks, Shawn; Hyman, Alexandra M; Aranda, Jorge; Chang, Bo; Bigelow, Chad E; and Rice, Dennis S, "ADIPOR1 is essential for vision and its RPE expression is lost in the Mfrp" (2018). Faculty Research 2018. 197. https://mouseion.jax.org/stfb2018/197 This Article is brought to you for free and open access by the Faculty Research at The ousM eion at the JAXlibrary. It has been accepted for inclusion in Faculty Research 2018 by an authorized administrator of The ousM eion at the JAXlibrary. For more information, please contact [email protected]. Authors Valentin M Sluch, Angela Banks, Hui Li, Maura A Crowley, Vanessa Davis, Chuanxi Xiang, Junzheng Yang, John T Demirs, Joanna Vrouvlianis, Barrett Leehy, Shawn Hanks, Alexandra M Hyman, Jorge Aranda, Bo Chang, Chad E Bigelow, and Dennis S Rice This article is available at The ousM eion at the JAXlibrary: https://mouseion.jax.org/stfb2018/197 www.nature.com/scientificreports OPEN ADIPOR1 is essential for vision and its RPE expression is lost in the Mfrprd6 mouse Received: 20 April 2018 Valentin M.
    [Show full text]
  • 1 and ET-3 Inhibit Estrogen and Camp Production by Rat Granulosa Cells in Vitro
    209 Endothelin (ET)-1 and ET-3 inhibit estrogen and cAMP production by rat granulosa cells in vitro A E Calogero, N Burrello and A M Ossino Division of Andrology, Department of Internal Medicine, University of Catania, 95123 Catania, Italy (Requests for offprints should be addressed to A E Calogero at Istituto di Medicina Interna e Specialita` Internistiche, Ospedale Garibaldi, Piazza S.M. di Gesu`, 95123 Catania, Italy) Abstract Endothelin (ET)-1 and ET-3, two peptides with a potent and a maximally stimulatory (3 mIU/ml) concentration of vasoconstrictive property, produce a variety of biological FSH. ET-1 and ET-3 dose-dependently suppressed basal effects in different tissues by acting through two different and FSH (1 mIU/ml)-stimulated cAMP production. ET-3 receptors, the ET-1 selective ETA receptor and the non- and SFX-S6c were significantly more potent than ET-1 in selective ETB receptor. An increasing body of literature suppressing estrogen production, suggesting that this effect suggests that ET-1 acts as a paracrine/autocrine regulator was not mediated by the ETA receptor. Indeed, BQ-123, of ovarian function. Indeed, ETB receptors have been a selective ETA receptor antagonist, did not influence identified in rat granulosa cells and ET-1 is a potent the inhibitory effects of ET-1 and ET-3 on basal and inhibitor of progesterone production. In contrast, incon- FSH-stimulated estrogen release. To determine a possible sistent data have been reported about the role of ET-1 on involvement of prostanoids, we evaluated the effects of estrogen production and the effects of ET-3 are not maximally effective concentrations of ET-1 and ET-3 on known.
    [Show full text]
  • Cooperation of Endothelin-1 Signaling with Melanosomes Plays a Role In
    © 2015. Published by The Company of Biologists Ltd | Biology Open (2015) 4, 1213-1221 doi:10.1242/bio.011973 RESEARCH ARTICLE Cooperation of endothelin-1 signaling with melanosomes plays a role in developing and/or maintaining human skin hyperpigmentation Daiki Murase1,2,*, Akira Hachiya1,*,‡, Mamiko Kikuchi-Onoe1, Rachel Fullenkamp2, Atsushi Ohuchi1, Takashi Kitahara1, Shigeru Moriwaki1, Tadashi Hase1 and Yoshinori Takema3 ABSTRACT both long-term sun-exposure and chronological aging. Such Skin hyperpigmentation is characterized by increased melanin hyperpigmentation is also thought to be related to the existence of synthesis and deposition that can cause significant psychosocial and uneven skin tones often observed on sun-exposed areas. Regardless of psychological distress. Although several cytokine-receptor signaling the significant psychosocial distress associated with age spots, little is cascades contribute to the formation of ultraviolet B-induced cutaneous known about the detailed mechanisms responsible for them, except for hyperpigmentation, their possible involvement in other types of skin ultraviolet B (UVB)-induced pigmentation, despite the fact that many hyperpigmentation has never been clearly addressed. Since our researchers have tried to identify the melanogenic stimulatory factor(s) continuous studies using skin specimens from more than 30 subjects involved. with ethnic skin diversity emphasized a consistent augmentation in the In the course of UVB-induced pigmentation, three major steps in expression of endothelin-1 (ET-1) and its receptor (Endothelin B the epidermis, melanocyte proliferation, activation of melanin receptor, ET-B) in hyperpigmented lesions, including senile lentigos synthesis and melanosome transfer to keratinocytes, have been (SLs), the precise function of ET-1 signaling was investigated in the reported to be responsible for the increased melanogenesis (Okazaki .
    [Show full text]
  • A 0.70% E 0.80% Is 0.90%
    US 20080317666A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0317666 A1 Fattal et al. (43) Pub. Date: Dec. 25, 2008 (54) COLONIC DELIVERY OF ACTIVE AGENTS Publication Classification (51) Int. Cl. (76) Inventors: Elias Fattal, Paris (FR); Antoine A6IR 9/00 (2006.01) Andremont, Malakoff (FR); A61R 49/00 (2006.01) Patrick Couvreur, A6II 5L/12 (2006.01) Villebon-sur-Yvette (FR); Sandrine A6IPI/00 (2006.01) Bourgeois, Lyon (FR) (52) U.S. Cl. .......................... 424/1.11; 424/423; 424/9.1 (57) ABSTRACT Correspondence Address: Drug delivery devices that are orally administered, and that David S. Bradlin release active ingredients in the colon, are disclosed. In one Womble Carlyle Sandridge & Rice embodiment, the active ingredients are those that inactivate P.O.BOX 7037 antibiotics, such as macrollides, quinolones and beta-lactam Atlanta, GA 30359-0037 (US) containing antibiotics. One example of a Suitable active agent is an enzyme Such as beta-lactamases. In another embodi ment, the active agents are those that specifically treat colonic (21) Appl. No.: 11/628,832 disorders, such as Chrohn's Disease, irritable bowel syn drome, ulcerative colitis, colorectal cancer or constipation. (22) PCT Filed: Feb. 9, 2006 The drug delivery devices are in the form of beads of pectin, crosslinked with calcium and reticulated with polyethylene imine. The high crosslink density of the polyethyleneimine is (86). PCT No.: PCT/GBO6/OO448 believed to stabilize the pectin beads for a sufficient amount of time such that a Substantial amount of the active ingredi S371 (c)(1), ents can be administered directly to the colon.
    [Show full text]
  • Nitric Oxide As a Second Messenger in Parathyroid Hormone-Related Protein Signaling
    433 Nitric oxide as a second messenger in parathyroid hormone-related protein signaling L Kalinowski, L W Dobrucki and T Malinski Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio, USA (Requests for offprints should be addressed to T Malinski, Department of Chemistry and Biochemistry, Ohio University, Biochemistry Research Laboratories 136, Athens, Ohio 45701–2979, USA; Email: [email protected]) (L Kalinowski was on sabbatical leave from the Department of Clinical Biochemistry, Medical University of Gdansk and Laboratory of Cellular and Molecular Nephrology, Medical Research Center of the Polish Academy of Science, Poland) Abstract Parathyroid hormone (PTH)-related protein (PTHrP) is competitive PTH/PTHrP receptor antagonists, 10 µmol/l produced in smooth muscles and endothelial cells and [Leu11,-Trp12]-hPTHrP(7–34)amide and 10 µmol/l is believed to participate in the local regulation of vascu- [Nle8,18,Tyr34]-bPTH(3–34)amide, were equipotent in lar tone. No direct evidence for the activation of antagonizing hPTH(1–34)-stimulated NO release; endothelium-derived nitric oxide (NO) signaling pathway [Leu11,-Trp12]-hPTHrP(7–34)amide was more potent by PTHrP has been found despite attempts to identify it. than [Nle8,18,Tyr34]-bPTH(3–34)amide in inhibiting Based on direct in situ measurements, it is reported here for hPTHrP(1–34)-stimulated NO release. The PKC inhibi- the first time that the human PTH/PTHrP receptor tor, H-7 (50 µmol/l), did not change hPTH(1–34)- and analogs, hPTH(1–34) and hPTHrP(1–34), stimulate NO hPTHrP(1–34)-stimulated NO release, whereas the release from a single endothelial cell.
    [Show full text]
  • Mechanisms of Skeletal Disease Mediated by Haematological
    OF z a ) n Mechanisms of Skeletal Disease Mediated by Haematolo gical Malignancies Beiqing Pan B. Med. M. Med. Sc. Matthew Roberts Laboratory, Hanson Institute, Institute of Medical and Veterinary Science Department of Medicine, The University of Adelaide, South Australia A thesis submitted to the University of Adelaide in candidature for the degree of Doctor of Philosophy August 2004 TABLE OF CONTENTS DEGLARAT|ON......... """' l AGKNOWLEDGMENT.............. """' ll A8STRACT............. """'lv ABBREVIATIONS """""v1 PUBLICATIONS """"""'xl CHAPTER 1 GENERAL INTRODUCTION ......1 TO BONE 1.1 HAEMATOLOGICAL MALIGNANCIES WHICII GIBE RISE 1 LESIONS 2 1.1.1 Osteolytic Bone Disease Mediated by Multiple Myeloma 2 1.1.1.1 General Description...'.. 4 t.l.l.2 P athophysiolo gy of tvttvt 5 1.1.1.3 Osteolytic Bone Disease Lt.2 Osteoblastic Bone Disease Mediated by POEMS" 6 t.l.2.1 General DescriPtion...... 6 l.l.2.2 Pathophysiology of POEMS Syndrome. 1 8 1.1.2.3 Osteoblastic Bone Disease 1.2 BONE PHYSIOLOGY.............. 8 1.2.1 PhysiologicalBoneRemodelling 9 1.2.2 Bone ResorPtion 9 1.2.2.1 Osteoclasts 9 1.2.2.2 Osteoclast Stem Cells 1.2.3 BoneFormation.......'......... 1.2.3.1 Osteoblast Cells 1.2.3.2 OsteoblastStemCells..... 1.2.3.3 OsteocYtes '.".....' 1.2.3.4 Lining Cells FACTORS INVOLVED IN BONE LESIONS... t4 1.3 l6 1.3.1 Osteoclast Activating Factors (OAFÐ """"' 1.3.1.1 Interleukin-1P 16 1.3.1.2 Interleukin-6 t7 l8 1 .3.1 .3 Tumour Necrosis Factor-cx'...... 1.3.1.4 ParathyroidHormone Related Protein""""""' t9 1.3.2 RANKL/RANIIOPGSYStem 20 1.3.2.1 GeneralDescriPtion 20 1.3.2.2 RANKL/OPG Ratio and Bone Lesion 22 1.3.2.3 Incrçased RANKL/OPG Ratio in MM"' 22 1.3.2.4 The Regulation of RANKL/OPG Ratio in MM 23 1.3.3 Endothelin-1 (ET-l)'..'.'...
    [Show full text]
  • A Focus on the Kisspeptin Receptor, Kiss1r
    Western University Scholarship@Western Electronic Thesis and Dissertation Repository 12-1-2014 12:00 AM Pathway-Specific Signaling and its Impact on erF tility: A Focus on the Kisspeptin Receptor, Kiss1r Maryse R. Ahow The University of Western Ontario Supervisor Dr. Andy Babwah The University of Western Ontario Graduate Program in Physiology A thesis submitted in partial fulfillment of the equirr ements for the degree in Doctor of Philosophy © Maryse R. Ahow 2014 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Molecular and Cellular Neuroscience Commons Recommended Citation Ahow, Maryse R., "Pathway-Specific Signaling and its Impact on erF tility: A Focus on the Kisspeptin Receptor, Kiss1r" (2014). Electronic Thesis and Dissertation Repository. 2537. https://ir.lib.uwo.ca/etd/2537 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. PATHWAY-SPECIFIC SIGNALING AND ITS IMPACT ON FERTILITY: A FOCUS ON THE KISSPEPTIN RECEPTOR, Kiss1r (Thesis format: Monograph) by Maryse R. Ahow Graduate Program in Physiology A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy The School of Graduate and Postdoctoral Studies The University of Western Ontario London, Ontario, Canada © Maryse R. Ahow, 2014 Abstract Hypothalamic gonadotropin-releasing hormone (GnRH) is the master regulator of the neuroendocrine reproductive (HPG) axis and its secretion is regulated by various afferent inputs to the GnRH neuron.
    [Show full text]
  • Endothelin-2 Deficiency Causes Growth Retardation, Hypothermia, and Emphysema in Mice
    Endothelin-2 deficiency causes growth retardation, hypothermia, and emphysema in mice Inik Chang, … , Roderick R. McInnes, Masashi Yanagisawa J Clin Invest. 2013;123(6):2643-2653. https://doi.org/10.1172/JCI66735. Research Article Endocrinology To explore the physiological functions of endothelin-2 (ET-2), we generated gene-targeted mouse models. GlobalE t2 knockout mice exhibited severe growth retardation and juvenile lethality. Despite normal milk intake, they suffered from internal starvation characterized by hypoglycemia, ketonemia, and increased levels of starvation-induced genes. Although ET-2 is abundantly expressed in the gastrointestinal tract, the intestine was morphologically and functionally normal. Moreover, intestinal epithelium–specific Et2 knockout mice showed no abnormalities in growth and survival. Global Et2 knockout mice were also profoundly hypothermic. Housing Et2 knockout mice in a warm environment significantly extended their median lifespan. However, neuron-specific Et2 knockout mice displayed a normal core body temperature. Low levels of Et2 mRNA were also detected in the lung, with transient increases soon after birth. The lungs ofE t2 knockout mice showed emphysematous structural changes with an increase in total lung capacity, resulting in chronic hypoxemia, hypercapnia, and increased erythropoietin synthesis. Finally, systemically inducible ET-2 deficiency in neonatal and adult mice fully reproduced the phenotype previously observed in global Et2 knockout mice. Together, these findings reveal that ET-2 is critical for the growth and survival of postnatal mice and plays important roles in energy homeostasis, thermoregulation, and the maintenance of lung morphology and function. Find the latest version: https://jci.me/66735/pdf Research article Endothelin-2 deficiency causes growth retardation, hypothermia, and emphysema in mice Inik Chang,1 Alexa N.
    [Show full text]
  • Endothelins (EDN1, EDN2, EDN3) and Their Receptors (EDNRA, EDNRB, EDNRB2) in Chickens Functional Analysis and Tissue Distributi
    General and Comparative Endocrinology 283 (2019) 113231 Contents lists available at ScienceDirect General and Comparative Endocrinology journal homepage: www.elsevier.com/locate/ygcen Endothelins (EDN1, EDN2, EDN3) and their receptors (EDNRA, EDNRB, EDNRB2) in chickens: Functional analysis and tissue distribution T ⁎ Haikun Liu, Qin Luo, Jiannan Zhang, Chunheng Mo, Yajun Wang, Juan Li Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, PR China ARTICLE INFO ABSTRACT Keywords: Endothelins (EDNs) and their receptors (EDNRs) are reported to be involved in the regulation of many phy- Chicken siological/pathological processes, such as cardiovascular development and functions, pulmonary hypertension, Endothelin neural crest cell proliferation, differentiation and migration, pigmentation, and plumage in chickens. However, Endothelin receptor the functionality, signaling, and tissue expression of avian EDN-EDNRs have not been fully characterized, thus Tissue expression impeding our comprehensive understanding of their roles in this model vertebrate species. Here, we reported the cDNAs of three EDN genes (EDN1, EDN2, EDN3) and examined the functionality and expression of the three EDNs and their receptors (EDNRA, EDNRB and EDNRB2) in chickens. The results showed that: 1) chicken (c-) EDN1, EDN2, and EDN3 cDNAs were predicted to encode bioactive EDN peptides of 21 amino acids, which show remarkable degree of amino acid sequence identities (91–95%) to their respective mammalian orthologs; 2) chicken (c-) EDNRA expressed in HEK293 cells could be preferentially activated by chicken EDN1 and EDN2, monitored by the three cell-based luciferase reporter assays, indicating that cEDNRA is a functional receptor common for both cEDN1 and cEDN2.
    [Show full text]
  • The Anti-Apoptotic Role of Neurotensin
    Cells 2013, 2, 124-135; doi:10.3390/cells2010124 OPEN ACCESS cells ISSN 2073-4409 www.mdpi.com/journal/cells Review The Anti-Apoptotic Role of Neurotensin Christelle Devader, Sophie Béraud-Dufour, Thierry Coppola and Jean Mazella * Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR 7275, Université de Nice-Sophia Antipolis, 660 route des Lucioles, Valbonne 06560, France; E-Mails: [email protected] (C.D.); [email protected] (S.B.-D.); [email protected] (T.C.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +33-4-93-95-77-61; Fax: +33-4-93-95-77-08. Received: 24 January 2013; in revised form: 15 February 2013 / Accepted: 26 February 2013 / Published: 4 March 2013 Abstract: The neuropeptide, neurotensin, exerts numerous biological functions, including an efficient anti-apoptotic role, both in the central nervous system and in the periphery. This review summarizes studies that clearly evidenced the protective effect of neurotensin through its three known receptors. The pivotal involvement of the neurotensin receptor-3, also called sortilin, in the molecular mechanisms of the anti-apoptotic action of neurotensin has been analyzed in neuronal cell death, in cancer cell growth and in pancreatic beta cell protection. The relationships between the anti-apoptotic role of neurotensin and important physiological and pathological contexts are discussed in this review. Keywords: neurotensin; receptor; apoptosis; sortilin 1. Introduction The tridecapeptide neurotensin (NT) was isolated from bovine hypothalami on the basis of its ability to induce vasodilatation [1]. NT is synthesized from a precursor protein following excision by prohormone convertases [2].
    [Show full text]